In the development of the immune system, T lymphocytes are derived from precursor stem cells which enter the thymus to undergo differentiation and maturation. T lymphocyte differentiation normally occurs via a series of discrete developmental stages involving an initial primitive progenitor cell without lymphocyte specific cell surface markers (CD34+ CD3− CD4− CD8−), followed by acquisition of lymphocyte specific markers and loss of CD34 (CD34− CD3+ CD4+ CD8+), followed by differentiation into mature CD3+ T cells expressing either CD4 or CD8 (CD3+ CD4+ CD8− or CD3+ CD4− CD8+).
While normal T cells are an integral part of mammalian immune responses, in some instances it is desirable to inhibit undesirable immune responses such as undesirable proliferation of T cells. For instance, autoimmune diseases are characterized as an immune reaction against “self” antigens. Autoimmune diseases include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and multiple sclerosis (MS). T cell responses have also been implicated in graft rejection and graft versus host disease (GVHD). Thus, treatment directed to inhibition of T cell differentiation would be greatly desired to treat such undesired immune responses.
There is a need for new compounds and methods for inhibiting T cell immune responses and for treating the above-noted diseases and conditions. By providing novel methods and compositions for modulating T cell development and functions, the instant invention fulfills this and other needs.